Malaria parasites are unable to synthesize purines de novo and rely on the host red blood cell as a source of these materials. The proposed program of study is designed to determine: 1. metabolic alterations taking place in the infected red cell that make purines available to the parasite, and 2. mechanisms whereby the intracellular parasite accumulates purines. Two hypotheses are being considered: 1. The growing intraerythrocytic parasite induces a drop in host cell pO2, which results in a decline in cellular ATP with the production of adenosine: this material, the preferred purine, is rapidly accumulated by the parasite. 2. Parasitization of the red cell induces changes in the fatty acid composition of the erythrocyte membrane which affects transport through the membrane. Studies to test these hypotheses will involve: (a) Determination of ATP levels as well as its degradation products in normal red cells, in red cells containing small uninucleate parasites and red cells containing large, multinucleate parasites; (b) assays for salvage pathway enzymes plus 5' nucleotidase activity; and (c) critical studies of purine transport by normal and malaria-infected erythrocytes and erythrocyte-free parasites; (d) simulation of parasite induced hypoxia in normal red cells by treatment with 0.2N NaCN or N2 or quinine followed by analyses as described under (a) yields (c). (e) Normal and infected red cells incubated in the presence and absence of cis-vaccenic and/or oleic acid will be analyzed as described under (a) yields (c). BIBLIOGRAPHIC REFERENCES: The ribosomes of the simian malaria Plasmodium knowlesi II. A cell-free protein synthesizing system. I.W. Sherman. Comp. Bioch. Physiol. 53B: 447-450 (1976). Protein synthesis by a cell-free preparation from the bird malaria, Plasmodium lophurae. I.W. Sherman and L.A. Jones. J. Protozool. 23(2): 277-281 (1976).